LAMR1 restricts Zika virus infection by attenuating the envelope protein ubiquitination

• Main Authors: Dingwen Hu, Yingchong Wang, Aixin Li, Qin Li, Caifeng Wu, Muhammad Adnan Shereen, Shanyu Huang, Kailang Wu, Ying Zhu, Wenbiao Wang, Jianguo Wu
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2021-01-01
• Series: Virulence
• Subjects: laminin receptor 1, lamr1; zika virus, zikv; e protein; ubiquitination; eukaryotic translation initiation factor 3 subunit 5, eif3s5
• Online Access: http://dx.doi.org/10.1080/21505594.2021.1948261
• ISSN: 2150-5594; 2150-5608

Zika virus (ZIKV) infection can cause severe neurological disorders, including Guillain–Barre syndrome and meningoencephalitis in adults and microcephaly in fetuses. Here, we reveal that laminin receptor 1 (LAMR1) is a novel host resistance factor against ZIKV infection. Mechanistically, we found that LAMR1 binds to ZIKV envelope (E) protein via its intracellular region and attenuates E protein ubiquitination through recruiting the deubiquitinase eukaryotic translation initiation factor 3 subunit 5 (EIF3S5). We further found that the conserved G282 residue of E protein is essential for its interaction with LAMR1. Moreover, a G282A substitution abolished the binding of E protein to LAMR1 and inhibited LAMR1-mediated E protein deubiquitination. Together, our results indicated that LAMR1 represses ZIKV infection through binding to E protein and attenuating its ubiquitination.